Substantial evidence suggests that the diversion of prescription drugs for non-medical use accounts for a rapidly increasing share of substances of abuse, particularly among high-risk youth and young adult populations. Yet, there is a scarcity of information about the use of these drugs, including what the substances are, how they are administered, and why they are initiated. Much of the available data on non-medical prescription drugs, which includes opioids, CMS depressants, and stimulants, is limited to survey data and older populations of users. Descriptive data is lacking about the non-medical use of prescription drugs among high-risk youth populations. We are proposing a two-city (New York and Los Angeles) comparative study of high-risk youth aged 16 to 25 who may be homeless, participating in the street economy, polydrug users and/or injection drug users. The project aims are to: describe why high-risk youth initiate non-medical prescription drug use;describe variability in the forms of prescription drugs available and behavioral practices employed in their administration;chart the social trajectory of the transition from prescription drug use into other types of controlled substances;and assess the consequences of chronic use of prescription drugs on increased risk for onset of behaviors associated with exposure to HIV and STIs. The project aims will be addressed during three study phases. Phase One will consist of a six month Community Assessment Process (CAP) to gather existing "local knowledge" about non-medical prescription drug use in each city. Phase Two will comprise a nine month qualitative study of 150 prescription drug users in New York and Los Angeles. Phase Three will constitute a 15 month cross-sectional, quantitative survey of 600 prescription drug users in New York and Los Angeles. Study findings will inform the development of a curriculum for community-based organizations aimed at reducing non-medical prescription drug use among high-risk youth. Public health research on non-medical prescription drug use is extremely limited, and little is currently known about how high-risk youth maintain healthy living standards in the face of their risky behavior. Results from the proposed study will fill a critical gap in the epidemiological literature on non-medical prescription drug use among high-risk youth who are at risk for negative health outcomes, including drug dependence, drug overdose, violence, victimization, and exposure to bloodborne pathogens.